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Investigating TP53 mutations in haematological malignancies: a central South African study

oncology
medical-genetics

Abstract

Background. Mutation of the tumour protein gene (TP53) is the most frequent genetic event in human cancer. TP53 is typically inactivated by allelic deletion (del17p13.1) or missense single-nucleotide substitutions in exons 5–8. TP53 mutations (TP53mut) are associated with adverse clinical outcomes, making screening crucial for the classification, prognostication, and personalised management of haematological malignancies. The frequency and clinical value of TP53mut in haematological malignancies in central South Africa remain undetermined due to limited test availability and high testing costs in a resource-restricted setting. This study aimed to determine the prevalence and disease association of TP53mut in haematological malignancies in a central South African population.

Methods. A cross-sectional analytical study design was followed. Sixty participants with various haematological malignancies were screened for del17p13.1 and exons 5–8 mutations, which were characterised. Fluorescent in situ hybridisation (FISH) was performed to detect del17p13.1, while TP53 exons 5–8 were analysed by means of standardised polymerase chain reaction (PCR) Sanger sequencing. The prevalence and clinical association of TP53mut with haematological malignancies were evaluated.

Results. TP53 mutations were prevalent in each malignancy investigated, with a higher-than-expected prevalence of 26.7%. TP53 mut was associated with adverse prognostic features overall. We found that double-hit TP53 mutants were associated with dismal clinical outcomes, and we identified a novel mutation in chronic lymphocytic leukaemia.

Conclusion. As the first study investigating TP53 mutations in haematological malignancies in South Africa, we provide a brief look into the prominence of TP53 mutations in this population and reiterate the importance of TP53 mutation screening in patient management.

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